Management of perioperative hypertension

ESCAPE: Design overview ESCAPE (Efficacy Study of Clevidipine Assessing its Perioperative Antihypertensive Effect in Cardiac Surgery) consists of two placebo-controlled trials with the same efficacy measures. ESCAPE-1 assessed the efficacy of clevidipine in treating preoperative hypertension in 105 patients. Eligible patients had a SBP of 160 mm Hg or higher and were clinically assessed as needing a reduction in SBP of 15% or more. ESCAPE-2 assessed the efficacy of clevidipine in treating postoperative hypertension in 110 patients.

ESCAPE-1: Rapid control of preoperative SBP Clevidipine was administered for at least 30 minutes and up to 1 hour before anesthesia induction in this trial. Results demonstrated a rapid onset on SBP lowering with only a modest increase in heart rate toward the end of the infusion.

ESCAPE: Clevidipine superior to placebo Results of both ESCAPE-1 and ESCAPE-2 were presented at the 56th Annual Meeting of the American Society of Anesthesiologists, 2007. BP reduction was achieved at a median time of 6 minutes (ESCAPE-1) and 5.3 minutes (ESCAPE-2), respectively. The median time for placebo was not estimable because too few patients in this group reached the prespecified target of a 15% reduction in SBP from baseline.

ECLIPSE program: Overview The ECLIPSE (Evaluation of Clevidipine in the Perioperative Treatment of Hypertension Assessing Safety Events) program is addressing gaps in the evidence base regarding perioperative BP control. Conducted in 1512 cardiac surgery patients, ECLIPSE has two objectives: Assess the relationship of BP to postoperative outcomes Compare different pharmacologic strategies for perioperative BP control

ECLIPSE: Comparison of safety endpoints by treatment Event rates for safety endpoints were similar in clevidipine and comparator groups in the individual arms of ECLIPSE.

ECLIPSE: Combined effects on primary safety endpoints Similar safety event rates were also observed when safety data for the clevidipine and comparator groups were combined.

BP control assessed via AUC analysis ECLIPSE investigators measured BP excursions above or below prespecified SBP limits. BP control was expressed as the cumulative area-under-the-curve (AUC) for these excursions.

ECLIPSE: Clevidipine vs comparators for perioperative BP control Clevidipine was associated with significantly better BP control than nitroglycerin and sodium nitroprusside, and with comparable BP control as nicardipine.

ECLIPSE: Relation of perioperative BP control to 30-day mortality Multiple logistic regression analysis was used to estimate the risk for different degrees of BP control. A 1 mm Hg excursion, if sustained for 60 minutes, was associated with a 20% increase in risk of death. Risk rose rapidly with each additional 1 mm Hg outside of the prespecified SBP range.

ECLIPSE: Predictors of postoperative renal dysfunction Further analysis of the ECLIPSE data showed that BP control was an independent risk factor for 30-day renal dysfunction (defined as a creatinine level of 2.0 mg/dL or greater, with a minimum increase of 0.7 mg/dL). Compared with a cumulative AUC in the first quartile, an AUC in the 4th quartile was associated with a 72.5% increase in risk.

ECLIPSE: Overview of perioperative BP control The data emerging from the ECLIPSE program suggest that perioperative BP control needs to be tighter than traditionally assumed, since even a 1 mm Hg excursion can be prognostically important, if sustained for 60 minutes or longer. The data also demonstrate the importance of avoiding “overshoot” when treating acute elevations in BP, since excursions below as well as above are prognostically important.

Summary: Acute hypertension Acute hypertension in nonsurgical patients has not been well studied in the past decade and there are multiple knowledge gaps, including: Patient characteristics Treatment patterns Outcomes Perioperative hypertension appears to be common, particularly in patients with pre-existing chronic hypertension and in relation to certain types of surgery. In addition, emerging data demonstrate importance of more stringent BP control than currently recommended by guidelines. Data from the ongoing STAT trial should provide insight into the long-term prognosis of patients with hypertensive urgencies/emergencies.